In practice, the use of analytical equipment for measuring various parameters of blood requires utilization of control materials which exhibit properties as close as possible to those observed in fresh normal human blood. By measuring known parameters of control materials, the instrumentation can be monitored to allow highly accurate measurements of patient blood samples.
It is generally accepted that the most effective approach to monitoring the reliability and accuracy of instruments that measure partial pressures of CO.sub.2 and O.sub.2 in blood is with the use of samples of fresh human blood which has been tonometered with gas mixes having known amounts of CO.sub.2, O.sub.2 and N.sub.2. Such a process is described by Burnett in Clinical Chemistry, 27(10):1761 (1981).
When the blood has been properly tonometered, the sample will have precise and fixed partial pressures of CO.sub.2 and O.sub.2. These prepared samples can then be introduced into the analytical instrument and pCO.sub.2 and pO.sub.2 values determined. Since the sample is identical to a patient blood specimen, but with known pCO.sub.2 and pO.sub.2 values, the instrument can be considered reliable for measuring unknown patient samples if the test values of the tonometered blood equal the theoretical values based on the gas mix used for tonometry.
Although the use of tonometered blood is considered to be ideal for monitoring blood gas instrumentation, the approach has a number of drawbacks which limit its use in all but a very small percentage of laboratories.
For example, materials derived from human sources are susceptible to infectious agents including hepatitis virus and HIV which can pose serious health hazards to laboratory personnel who must perform the tonometry and testing of the sample. In addition, the instruments commonly used to measure pCO.sub.2 and pO.sub.2 also measure blood pH. Since the tonometered blood does not have a known pH value, the sample cannot be used for monitoring the pH measurements and a separate pH control standard must be used.
Similarly, many laboratories that perform measurements of pCO.sub.2, pO.sub.2 and pH on blood samples also measure total hemoglobin and hemoglobin fractions on a CO-Oximeter that is located near the blood gas instrument. However, since the blood used for tonometry is acquired from random patient samples, the tonometered sample has no known hemoglobin value, and therefore it is not useful for monitoring the CO-Oximeter. Consequently, a separate control standard is required for this instrument also.
Finally, the entire procedure for properly preparing tonometered blood samples requires disciplined techniques and many laboratories lack trained personnel as well as the time to prepare the samples.
Because of these disadvantages, most laboratories use control standards which mimic human blood but have properties quite different than fresh blood. For example, buffered aqueous solutions which have been tonometered with CO.sub.2 and O.sub.2 are often used. These materials are assayed for predetermined values for pH, pCO.sub.2 and pO.sub.2. However, in composition, physical properties and chemical properties they differ greatly from whole blood.
Other control standards comprise buffered suspensions of modified human red blood cells or hemoglobin solutions prepared from lysed red blood cells. These materials have some properties which more closely approximate actual blood than do the aqueous based controls, but their pO.sub.2 buffering action and inability to provide the O.sub.2 saturation characteristics of fresh blood, cause these materials to perform more like aqueous solutions than tonometered fresh blood. Furthermore, since they are prepared from human blood, the health risk to technicians is not eliminated.
In summary, the commercial blood gas controls which are used instead of tonometered fresh human blood are generally considered a compromise between convenience, economy and the ideal control standard.
Thus, a need exists for a non-hazardous material which can be packaged to eliminate the sample collection and preparation steps necessary when blood samples are used, is stable in the packaged form, and can be tonometered in the same manner as is practiced with fresh human blood to provide a control standard that has O.sub.2 saturation characteristics and other properties similar to fresh human blood, but unlike the blood samples, will have predetermined pH and hemoglobin values for monitoring the instrument performance in the measurement of these parameters as well as pO.sub.2 and pCO.sub.2.
Although some of the commercial blood based materials can be used as prepackaged fluids for tonometry, the inability of these materials to be manufactured and stored without the oxidation of a significant percent of the hemoglobin to methemoglobin (which does not bind with oxygen), causes the solution to lose the oxygen saturation properties of fresh blood, and therefore makes the material unsuitable as a substitute for blood as a tonometry solution.
Attempts to provide a system for reducing methemoglobin content in a blood-based material have been the subject of a variety of scientific studies. For example, in U.S. Pat. No. 4,485,174 to Chiang et al., a "methemoglobin reductase" enzyme system is described as a means for maintaining a low methemoglobin level. This system, however, has demonstrated only limited usefulness, since the supply of methemoglobin reducing reagents can be exhausted when the hemoglobin solution is stored under an oxygen containing atmosphere.
Other blood-gas control solutions and methods have been described in U.S. Pat. No. 3,859,049; U.S. Pat. No. 3,973,913; U.S. Pat. No. 4,001,142; and U.S. Pat. No. 4,469,792. Additionally, a blood-gas control solution and method has been described by Steiner et al., Clinical Chemistry, 24, 793 (1978). Each of these, however, described a control standard having a limited storage life and/or a chemical formulation which provides physiologically inaccurate values.
Thus, a need still exists for a blood-based reference solution which, after equilibration with an appropriate gas mixture, can be used to monitor blood-gas analysis equipment. The reference solution should preferably have an extended storage life, provide physiologically accurate blood-gas values, and provide uniform values among a large number of samples.